This invention relates generally to sensors and sensor systems for detecting analytes in fluids and, more particularly, to sensor systems that incorporate sensors having electrical properties that vary according to the presence and concentration of analytes, and to methods of using such sensor systems.
There is considerable interest in developing sensors that act as analogs of the mammalian olfactory system (Lundstrom et al., Nature 1991, 352, 47-50; Shurmer et al., Sens. Act. B 1992, 8, 1-11; Shurmer et al., Sens. Actuators B 1993, 15, 32). Prior attempts to produce broadly responsive sensors and enhanced sensor arrays have exploited heated metal oxide thin film resistors (Gardner et al., Sens. Act. B 1991, 4, 117-121; Gardner et al., Sens. Act. B 1991, 6, 71-75), polymer sorption layers on the surfaces of acoustic wave (SAW) resonators (Grate et al., Sens. Act. B 1991, 3, 85-111; Grate et al., Anal. Chem. 1993, 65, 1868-1881), arrays of electrochemical detectors (Stetter et al., (1986) Anal. Chem. 1986, 58, 860-866; Stetter et al., Sens. Act. B 1990, 1, 43-47; Stetter et al., Anal. Chem. Acta 1993, 284, 1-11), conductive polymers or composites that consist of regions of conductors and regions of insulating organic materials (Pearce et al., Analyst 1993, 118, 371-377; Shurmer et al., Sens. Act. B 1991, 4, 29-33; Doleman et al., Anal. Chem. 1998, 70, 2560-2654; Lonergan et al., Chem. Mater. 1996, 8, 2298). Arrays of metal oxide thin film resistors, typically based on tin oxide (SnO2) films that have been coated with various catalysts, yield distinct, diagnostic responses for several vapors (Corcoran et al., Sens. Act. B 1993, 15, 32-37). Surface acoustic wave resonators are extremely sensitive to both mass and acoustic impedance changes of the coatings in array elements, but the signal transduction mechanism involves somewhat complicated electronics, requiring frequency measurement to 1 Hz while sustaining a 100 MHZ Rayleigh wave in the crystal. Attempts have also been made to construct arrays of sensors with conducting organic polymer elements that have been grown electrochemically through use of nominally identical polymer films and coatings. Moreover, Pearce et al., Analyst 1993, 118, 371-377, and Gardner et al., Sens. Act. B 1994, 18-19, 240-43 describe, polypyrrole based sensor arrays for monitoring beer flavor. U.S. Pat. No. 4,907,441, describes general sensor arrays with particular electrical circuitry. U.S. Pat. No. 4,674,320 describes a single chemoresistive sensor having a semi-conductive material selected from the group consisting of phthalocyanine, halogenated phthalocyanine and sulfonated phthalocyanine, which was used to detect a gas contaminant. Other gas sensors have been described by Dogan et al., Synth. Met. 1993, 60, 27-30, and Kukla, et al., Films. Sens. Act. B., Chemical 1996, 37, 135-140. Each of the above-cited references is incorporated by reference herein.
Volatile sulfur compounds stand out in that humans are far more sensitive to these vapors than to analogous alcohols, alkanes, ketones, or esters, for example. Humans have odor detection thresholds for volatile sulfur compounds in the part per billion (ppb) range. Thiols are consumed in many foods and the liver is responsible for eliminating them from the body. Reports have shown elevated levels of several volatile sulfur compounds in the lung air of patients with various disease states. An electronic nose with high sensitivity for thiols could thus sense and discriminate these molecules, potentially providing a simple method for diagnosis of these diseases.
However, an electronic nose formed from composites conductors and insulating organic materials does not display the enhanced sensitivity to thiols, relative to analogous alcohols or ketones for example, that humans possess. A similar phenomenon occurs for biogenic amines, where humans have enhanced sensitivity relative to that displayed from sensors that use arrays of composites formed from regions of conductors and regions of insulating organic material. Thus, there remains a need for sensors having enhanced sensitivity for thiols and other organic compounds.
The invention provides sensing apparatus, including sensors and sensor arrays, and methods for detecting a chemical analyte, in particular a thiol-containing analyte, in a fluid.
In general, in one aspect, the invention provides sensors, sensor arrays and sensing methods implementing techniques for detecting chemical analytes in fluids. One or more sensors are provided, which include regions of conductive material and regions of nonconductive material proximate to the conductive material. The nonconductive material includes a chemical group coupled to the conductive material. The chemical group is displaceable by a chemical analyte. The sensors are exposed to a fluid containing the chemical analyte under conditions sufficient to cause the chemical analyte to displace the chemical group. A response is measured based on the displacement of the chemical group. The chemical analyte is detected based on the measured response.
Particular implementations may include one or more of the following features. The conductive material can include a plurality of particles, which can include one or more metals or metal alloys. The particles can include a metal core. The chemical group can be a ligand covalently coupled to the metal core. In a preferred embodiment, the chemical analyte is a thiol, the metal core includes gold or silver, and the chemical group is an alkylamine. The particles can be disposed in a polymer matrix, which can include a conducting, semiconducting, or insulating organic polymer. The response can include a change in conductivity, resistance, impedance, capacitance, inductance, or optical properties of one or more of the sensors, or a combination thereof, upon exposure of the sensors to the chemical analyte. If the chemical analyte is smaller than the size of the chemical group, the response can be measured as a decrease in resistance or an increase in conductivity resulting from displacement of the chemical group by the chemical analyte. The nonconductive material can include a plurality of chemical groups coupled to the conductive material. The plurality of chemical groups can include a plurality of different chemical groups. The sensors can be exposed to the fluid containing the chemical analyte under conditions sufficient to cause the chemical analyte to displace a first portion of the plurality of chemical groups, such that the conductive material remains coupled to one or more remaining portions of the plurality of chemical groups. A second chemical analyte, which may be the same as or different from the first analyte, can be detected by exposing the sensors to a fluid containing the second chemical analyte under conditions sufficient to cause the second chemical analyte to displace one or more remaining portions of the plurality of chemical groups, and measuring a response based on the displacement of the one or more remaining portions of the plurality of chemical groups. The sensors can include a plurality of different sensors, and can take the form of a sensor array. The sensor array can include two or more sensors that include different conductive materials or chemical groups. The chemical analyte can be detected based on a different response measured for each of a plurality of the different sensors.
In general, in another aspect, the invention provides further sensors, sensor arrays and sensing methods for detecting a chemical analyte in a fluid. One or more sensors are provided, which include a plurality of conductive particles disposed in a nonconductive matrix. The conductive particles include a metallic core. The sensors are exposed to a fluid containing a chemical analyte under conditions sufficient to cause the chemical analyte to react with the metallic core to form a capped particle. A response is measured based on the reaction of the chemical analyte and the metallic core. The chemical analyte is detected based on the measured response.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.